EMTRICITABINE; TENOFOVIR ALAFENAMIDE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that is phosphorylated to emtricitabine triphosphate, which competes with the natural substrate deoxycytidine 5'-triphosphate and inhibits HIV-1 reverse transcriptase by incorporating into viral DNA, causing chain termination. Tenofovir alafenamide is a prodrug of tenofovir, an NRTI; it is converted to tenofovir, then phosphorylated to tenofovir diphosphate, which inhibits HIV-1 reverse transcriptase by competing with deoxyadenosine 5'-triphosphate and causing DNA chain termination.
| Metabolism | Emtricitabine: undergoes limited metabolism; approximately 86% excreted unchanged in urine. Tenofovir alafenamide: hydrolyzed intracellularly to tenofovir by cathepsin A and CES1; tenofovir is phosphorylated to tenofovir diphosphate; tenofovir is eliminated renally via glomerular filtration and active tubular secretion. |
| Excretion | Emtricitabine: 86% renal (active tubular secretion and glomerular filtration), 14% fecal. Tenofovir alafenamide: <1% renal, >97% fecal (as unchanged drug or metabolites, primarily via hepatobiliary excretion). |
| Half-life | Emtricitabine: 10 hours (prolonged to ~40 hours in severe renal impairment, CrCl <30 mL/min). Tenofovir alafenamide: 0.51 hours (active metabolite tenofovir diphosphate has intracellular half-life of 150-180 hours in PBMCs, supporting once-daily dosing). |
| Protein binding | Emtricitabine: <4% (minimal). Tenofovir alafenamide: ~80% (to plasma proteins, likely albumin). |
| Volume of Distribution | Emtricitabine: 1.3 L/kg (distributes into total body water). Tenofovir alafenamide: 0.07 L/kg (confined to plasma and interstitial fluid; limited tissue distribution but efficiently loads PBMCs). |
| Bioavailability | Oral: Emtricitabine 93% (capsule) and 100% (tablet). Tenofovir alafenamide bioavailability is approximately 40% (enhanced by food; high-fat meal increases exposure by 50-80%). |
| Onset of Action | Oral: Emtricitabine and tenofovir alafenamide reach peak plasma concentrations at 1-2 hours and 0.5-1 hour, respectively. Clinical antiviral effect is detectable within 2-4 weeks. |
| Duration of Action | Antiretroviral effect persists for 24 hours with once-daily dosing, supported by long intracellular half-life of tenofovir diphosphate. Duration correlates with intracellular concentrations; trough levels maintain efficacy. |
One tablet orally once daily containing emtricitabine 200 mg and tenofovir alafenamide 25 mg.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with CrCl <15 mL/min. For CrCl 15–29 mL/min: one tablet every 24 hours. For CrCl 30–59 mL/min: no adjustment needed. For CrCl >=60 mL/min: no adjustment needed. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended for severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | For patients weighing >=35 kg: one tablet (200 mg/25 mg) orally once daily. For patients weighing >=25 kg to <35 kg: one tablet (200 mg/25 mg) orally once daily (based on available formulations; lower strength tablets may be used if appropriate). |
| Geriatric use | No specific dose adjustment based on age alone. Monitor renal function due to age-related decline in CrCl. Use same dosing as adults with renal adjustment as per GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Breastfeeding | Emtricitabine and tenofovir alafenamide are excreted into human breast milk at low concentrations. M/P ratio not established. Risk of HIV transmission via breastfeeding outweighs benefits in HIV-positive mothers; recommend avoidance. For HBV, consider risk-benefit. |
| Teratogenic Risk | First trimester: Limited human data; no increased risk of major birth defects observed. Second and third trimester: No evidence of fetal toxicity in animal studies. Placental transfer occurs in humans. Cases of lactic acidosis/hepatomegaly with steatosis reported in pregnant women on nucleoside analogues. |
■ FDA Black Box Warning
Posttreatment acute exacerbation of hepatitis B: Discontinuation of emtricitabine/tenofovir alafenamide may result in severe acute exacerbations of hepatitis B in patients coinfected with HIV-1 and HBV. Monitor hepatic function closely for at least several months after stopping treatment. Lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogs, including tenofovir alafenamide.
| Common Effects | Hepatitis B |
| Serious Effects |
["Prior hypersensitivity to emtricitabine, tenofovir alafenamide, or any other component.","Use for PrEP in individuals with unknown or positive HIV-1 status (not contraindicated per se but not recommended due to resistance risk; same contraindication as HIV-1 infection)."]
| Precautions | ["Risk of lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, especially in obese patients or those with prolonged nucleoside exposure.","Exacerbation of hepatitis B after discontinuation (black box warning).","Renal impairment: tenofovir alafenamide is associated with a lower risk of renal toxicity compared to tenofovir disoproxil fumarate, but renal monitoring is recommended; avoid or adjust dose in severe renal impairment (CrCl <15 mL/min).","Bone effects: tenofovir alafenamide may cause decreased bone mineral density; monitor in patients with history of fracture or osteoporosis risk.","Immune reconstitution syndrome: including inflammatory responses to opportunistic infections.","Lipid effects: tenofovir alafenamide is associated with increased total cholesterol and LDL, but with a favorable lipid profile compared to tenofovir disoproxil fumarate.","Not recommended for use as PrEP in individuals with unknown or positive HIV-1 status (due to risk of resistance)."] |
Loading safety data…
| Fetal Monitoring | Monitor hepatic function, renal function (serum creatinine, urine glucose/protein), and lactic acid levels. Assess fetal growth via ultrasound. Screen for HBV and HIV with viral load monitoring. |
| Fertility Effects | No significant effect on fertility in animal studies. Human data limited; no evidence of impaired fertility in men or women. |
| Food/Dietary | No significant food interactions; can be taken with or without food. However, high-fat meals may slightly increase absorption of TAF (not clinically relevant). Avoid concurrent use of nephrotoxic drugs (e.g., NSAIDs, aminoglycosides, IV contrast) without monitoring. |
| Clinical Pearls | Monitor renal function (serum creatinine, estimated GFR, urinalysis) before initiating therapy and routinely during treatment; avoid if eGFR < 30 mL/min unless on chronic hemodialysis. Test for hepatitis B virus (HBV) infection before starting; severe acute exacerbations of HBV may occur upon discontinuation in co-infected patients. Emtricitabine/tenofovir alafenamide (TAF) has less renal and bone toxicity compared to tenofovir disoproxil fumarate (TDF). Assess for HIV pre-exposure prophylaxis (PrEP) indications: sexually active adults at high risk; confirm HIV-negative status immediately before initiation and at least every 3 months. |
| Patient Advice | Take one tablet orally once daily with or without food. · Do not miss doses; if missed, take as soon as remembered unless it is close to the next dose, then skip the missed dose. · This medication does not cure HIV or prevent transmission; continue safer sex practices. · You will need regular blood tests to monitor kidney function and HIV status. · If you have hepatitis B, do not stop this medication without consulting your doctor; stopping can cause severe liver problems. · Report symptoms of lactic acidosis (unusual muscle pain, trouble breathing, stomach pain with nausea/vomiting) or liver problems (dark urine, yellowing eyes/skin). · Keep tablets in original container; do not store in pill boxes for more than 30 days. · Inform all healthcare providers that you are taking this medication. |